PMID- 20885442
OWN - NLM
STAT- MEDLINE
DCOM- 20110531
LR  - 20211020
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 18
IP  - 3
DP  - 2011 Mar
TI  - miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial 
      alterations associated with modulation of HIF-1 activity.
PG  - 465-78
LID - 10.1038/cdd.2010.119 [doi]
AB  - Following the identification of a set of hypoxia-regulated microRNAs (miRNAs), 
      recent studies have highlighted the importance of miR-210 and of its 
      transcriptional regulation by the transcription factor hypoxia-inducible factor-1 
      (HIF-1). We report here that miR-210 is overexpressed at late stages of non-small 
      cell lung cancer. Expression of miR-210 in lung adenocarcinoma A549 cells caused 
      an alteration of cell viability associated with induction of caspase-3/7 
      activity. miR-210 induced a loss of mitochondrial membrane potential and the 
      apparition of an aberrant mitochondrial phenotype. The expression profiling of 
      cells overexpressing miR-210 revealed a specific signature characterized by 
      enrichment for transcripts related to 'cell death' and 'mitochondrial 
      dysfunction', including several subunits of the electron transport chain (ETC) 
      complexes I and II. The transcript coding for one of these ETC components, SDHD, 
      subunit D of succinate dehydrogenase complex (SDH), was validated as a bona fide 
      miR-210 target. Moreover, SDHD knockdown mimicked miR-210-mediated mitochondrial 
      alterations. Finally, miR-210-dependent targeting of SDHD was able to activate 
      HIF-1, in line with previous studies linking loss-of-function SDH mutations to 
      HIF-1 activation. miR-210 can thus regulate mitochondrial function by targeting 
      key ETC component genes with important consequences on cell metabolism, survival 
      and modulation of HIF-1 activity. These observations help explain contradictory 
      data regarding miR-210 expression and its putative function in solid tumors.
FAU - Puissegur, M-P
AU  - Puissegur MP
AD  - Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UMR6097, Sophia 
      Antipolis, France.
FAU - Mazure, N M
AU  - Mazure NM
FAU - Bertero, T
AU  - Bertero T
FAU - Pradelli, L
AU  - Pradelli L
FAU - Grosso, S
AU  - Grosso S
FAU - Robbe-Sermesant, K
AU  - Robbe-Sermesant K
FAU - Maurin, T
AU  - Maurin T
FAU - Lebrigand, K
AU  - Lebrigand K
FAU - Cardinaud, B
AU  - Cardinaud B
FAU - Hofman, V
AU  - Hofman V
FAU - Fourre, S
AU  - Fourre S
FAU - Magnone, V
AU  - Magnone V
FAU - Ricci, J E
AU  - Ricci JE
FAU - Pouyssegur, J
AU  - Pouyssegur J
FAU - Gounon, P
AU  - Gounon P
FAU - Hofman, P
AU  - Hofman P
FAU - Barbry, P
AU  - Barbry P
FAU - Mari, B
AU  - Mari B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101001
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN210 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 7)
SB  - IM
MH  - Apoptosis
MH  - Carcinoma, Non-Small-Cell Lung/enzymology/*genetics/pathology/ultrastructure
MH  - Caspase 3/metabolism
MH  - Caspase 7/metabolism
MH  - Cell Hypoxia/genetics
MH  - Cell Line, Tumor
MH  - Cell Survival/genetics
MH  - Down-Regulation/genetics
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Lung Neoplasms/enzymology/*genetics/pathology/ultrastructure
MH  - MicroRNAs/antagonists & inhibitors/genetics/*metabolism
MH  - Mitochondria/enzymology/*pathology/ultrastructure
MH  - Mitochondrial Proteins/metabolism
MH  - Neoplasm Staging
MH  - Phenotype
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Succinate Dehydrogenase/metabolism
MH  - Up-Regulation/genetics
PMC - PMC3131992
EDAT- 2010/10/05 06:00
MHDA- 2011/06/01 06:00
PMCR- 2012/03/01
CRDT- 2010/10/02 06:00
PHST- 2010/10/02 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/06/01 06:00 [medline]
PHST- 2012/03/01 00:00 [pmc-release]
AID - cdd2010119 [pii]
AID - 10.1038/cdd.2010.119 [doi]
PST - ppublish
SO  - Cell Death Differ. 2011 Mar;18(3):465-78. doi: 10.1038/cdd.2010.119. Epub 2010 
      Oct 1.